title: Identification of a mitotic death signature in cancer cell lines.
abstract: This study examined the molecular mechanism of action of anti-mitotic drugs. The hypothesis was tested that death in mitosis occurs through sustained mitotic arrest with robust Cdk1 signaling causing complete phosphorylation of Mcl-1 and Bcl-xL, and conversely, that mitotic slippage is associated with incomplete phosphorylation of Mcl-1/Bcl-xL. The results, obtained from studying six different cancer cell lines, strongly support the hypothesis and identify for the first time a unique molecular signature for mitotic death. The findings represent an important advance in understanding anti-mitotic drug action and provide insight into cancer cell susceptibility to such drugs which has important clinical implications.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Nandini
authors.initials: N
authors.lastname: Sakurikar
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Eichhorn
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Alford
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: chamberstimothyc@uams.edu.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Chambers
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008938:Mitosis / Q000187:drug effects; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D051020:bcl-X Protein; D016203:CDC2 Protein Kinase; D002945:Cisplatin
keywords: Apoptosis; Bcl-2 proteins; Cancer cell lines; Mitotic arrest; Mitotic death; Phosphorylation